The broad, long-term objective of this program of research is to better understand the effects of hormone therapy (HT) and alternative botanical supplements on cognition and brain functioning in early postmenopausal women. The specific aims of this research project are to quantify and compare the effects of the botanical menopausal treatments, black cohosh and red clover, and standard HT, Prempro (r) (conjugated equine estrogen plus medroxyprogesterone acetate), on neuropsychological and neuroimaging outcomes. The proposed design is a randomized, double-blind, placebo-controlled clinical trial. The cognitive study is conducted as an ancillary study to the NIH-funded study, A Phase II, Randomized, Double -Blind, Placebo-Controlled Study to Determine the Efficacy of Black Cohosh, Red Clover and Prempro(r) in the Management of Hot Flashes. Participants will include up to 28 women in each study arm - placebo, Prempro(r), black cohosh, and red clover - for a total n of up to 112. The primary outcome measures will be scores on standardized neuropsychological tests and patterns of brain activation during performance of verbal memory [unreadable] tests. Before treatment and at the end of the 12-month treatment period, participants will complete a 1.5- hour battery of neuropsychological tests that have been shown in previous studies to be sensitive to the effects of HT and menopausal symptoms. Half of the participants (n = 60) will also complete neuroimaging assessments using functional magnetic resonance imaging (fMRI) before and after the 12-month treatment period. The tasks performed in the MRI scanner will be verbal and figural memory tasks shown to be sensitive to HT in midlife women. Findings of group differences in the patterns of brain activation (i.e., regional blood flow changes) will point to the brain areas subserving any treatment-related improvements in memory performance. Recent findings of significant health risks associated with Prempro heighten the need for research into the effects of alternative therapies for menopausal symptoms on cognitive outcomes. [unreadable] [unreadable]